Our long term objective is to develop clinically useful reagents for the identification in stained blood smears of functionally distinct lymphocyte subpopulations (LYSP) in patients with malignancies. We started from our observation that some bacteria bind naturally to human LYSP and help identify them in blood smears. Burcella melitensis was found to bind B cells, normal or leukemic; also, two B and four T LYSP could be identified by their binding of different bacteria. It appears that B. melitensis also binds to pre B cells and we propose to classify some the "null" cell leukemias by using this marker. Based on a newly developed procedure, we shall try to obtain by mutation and selection from an Escherichia coli strain, bacteria that bind to activated T cells. We found that LYSP of normal donors bind consistantly certain bacteria and that changes can be detected in cancer patients that, we assume, are caused primarily by tumor load. Thus, we shall determine the normal values for LYSP and their changes in cancer patients, particularly as prognostic indicators. In patients with chronic lymphocytic leukemia, we determined that the binding of bacteria to leukemic lymphocytes (CLL) can be correlated with the clinical status. The prognostic and therapy indicating value of the test for CLL patients will be investigated based on the hypothesis that malignant B cells with poor binding capacity for bacteria have a selective advantage over hosts defense systems. This is based on our experiments which suggest that the mechanism of binding of bacteria involves an interaction between a carbohydrate on the bacteria and a "lectin" on the lymphocyte. These lectins may be involved in the functions of LYSP and attempts will be made to isolte them from activated T cells as well as the "complementary" carbohydrate structure on the bacteria. Some of the LYSP were separated by adherence so bacterial monolayers and functional differences were demonstrated in mitogen responses, specific cytotoxicity, natural killing activity, antibody-dependent cellular cytotoxicity, and "suppression" of natural killer cells. Other functional differences between LYSP identified by bacterial adherence such as help or suppression in antibody formation, antibody secretion by B cells etc. will be investigated. We shall also study the relationship between LYSP identified by bacteria and by monoclonal antibodies.